p-Chloro-diphenyl diselenide, an organoselenium compound, with antidepressant-like and memory enhancer actions in aging male rats
p-Chloro-diphenyl diselenide, an organoselenium compound, with antidepressant-like and memory enhancer actions in aging male rats
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DOI：
10.1007/s10522-011-9369-9
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发表时间：
2012-06-01
期刊：
影响因子：
4.5
通讯作者：
Nogueira, Cristina W.
中科院分区：
文献类型：
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作者：
Bortolatto, Cristiani F.;Wilhelm, Ethel A.;Nogueira, Cristina W.
本研究旨在评价对氯二苯基二硒醚（p-ClPhSe）（2）对雄性大鼠抑郁样行为和衰老所致认知障碍的保护作用。为此，老年大鼠口服（p-ClPhSe）（2）（10或25 mg/kg）7天。然后，对大鼠进行遗忘、记忆和抑郁实验模型的测试。此外，还测定了大鼠皮层和海马Na+ K+ ATP酶活性和反应物质（RS）水平。我们的研究结果表明，（p-ClPhSe）（2）（10和25 mg/kg）治疗老年大鼠在物体定位试验中的空间记忆缺陷和强迫游泳试验（FST）中的抑郁样行为逆转了衰老引起的。在旷场试验中，由于年龄增长引起的探索行为（勃起）的减少并没有被（p-ClPhSe）（2）给药所改变。此外，最高剂量的（p-ClPhSe）（2）可恢复衰老引起的皮质和海马RS水平的升高和Na+ K+ ATP酶活性的抑制。评估抗抑郁样作用的机制（p-ClPhSe）（2），老年大鼠接受WAY 100635（0.1 mg/kg，皮下注射，选择性5-HT 1AR拮抗剂），利坦色林（1 mg/kg，腹膜内，5-HT 2A/2CR拮抗剂）或昂丹司琼（1 mg/kg，腹膜内，5-HT 3R拮抗剂）（2）（25 mg/kg）处理前15分钟。30 min后，进行FST。结果表明，除了抗氧化作用外，5-HT 1A和5-HT 3受体的调节可能至少部分参与了（p-ClPhSe）（2）在老年大鼠中引起的抗抑郁样作用。这些发现强调了（p-ClPhSe）（2）在老年雄性大鼠中的有益潜力。
The aim of this study was to evaluate the protective effects of p-chloro-diphenyl diselenide (p-ClPhSe)(2) on depressant-like action and cognitive impairment caused by aging in male rats. For this purpose, old rats were orally treated with (p-ClPhSe)(2) (10 or 25 mg/kg) for seven days. Then, rats were tested in experimental models of ambulation, memory and depression. In addition, Na+ K+ ATPase activity and reactive species (RS) levels were measured in rat cortex and hippocampus. Our findings demonstrated that treatment of old rats with (p-ClPhSe)(2) (10 and 25 mg/kg) reversed spatial memory deficit in the object location test and depressant-like action in the forced swimming test (FST) caused by aging. Reduction in exploratory behavior (rearings) in the open-field test caused by aging was not altered by (p-ClPhSe)(2) administration. Moreover, the increase of RS levels and inhibition of Na+ K+ ATPase activity in cortex and hippocampus resulting from aging were restored by the highest dose of (p-ClPhSe)(2). To assess the mechanisms involved in the antidepressant-like effect of (p-ClPhSe)(2), old rats received WAY100635 (0.1 mg/kg, subcutaneous, a selective 5-HT1AR antagonist), ritanserin (1 mg/kg, intraperitoneal, a 5-HT2A/2CR antagonist) or ondansetron (1 mg/kg, intraperitoneal, a 5-HT3R antagonist) 15 min before (p-ClPhSe)(2) (25 mg/kg) treatment. After 30 min, the FST was performed. Results showed that in addition to the antioxidant action, the modulation of 5-HT1A and 5-HT3 receptors may be at least partly involved in the antidepressant-like action elicited by (p-ClPhSe)(2) in old rats. These findings highlight the beneficial potential of (p-ClPhSe)(2) in aged male rats.